长链非编码RNA HIF1a-AS1通过调节内皮细胞功能影响动脉粥样硬化发病的机制研究

Long non-coding RNAs (lncRNAs) play important roles in various biological processes and are also associated with a wide range of diseases. HIF 1 alpha-antisense RNA 1 (HIF1a-AS1) has been shown to regulate vascular smooth muscle cell proliferation and apoptosis. However, little is known about the function of HIF 1 alpha-antisense RNA 1 (HIF1a-AS1) in regulating endothelial cells differentiation in cardiovascular disease. This proposal aims to determine the consequence of HIF1a-AS1 dysfunction in the endothelial cell proliferation, migration, adhesion and apoptosis. Moreover the expression of HIF1a-AS1 will be detected in control and cardiovascular disease samples. Furthermore, this proposal will also focus on revealing molecular mechanism of HIF1a-AS1 by identifying the promoter, the binding partner and the signaling pathway of HIF1a-AS1. This study will identify a potential lncRNA target for cardiovascular disease and will greatly facilitate therapeutic treatment of cardiovascular disease.

长链非编码RNA（lncRNA）在生物体的生命活动中发挥着极广泛的调控作用，并参与了多种疾病的发生和发展。本课题组前期研究已证明一个新的lncRNA在心血管系统高表达，并影响血管平滑肌细胞的正常生理功能。缺氧诱导因子-1(HIF1a) 在心血管系统中起重要的调控作用，已有研究表明HIF1a的一个反义转录物( HIF1a-AS1)可以调节血管平滑肌细胞的增殖和凋亡。为了揭示HIF1a-AS1在调节内皮细胞正常生物学功能，及其在动脉粥样硬化中的作用，本项目拟通过研究1）敲除HIF1a-AS1对人脐静脉内皮细胞增殖，迁移，粘附和凋亡的影响；2）检测HIF1a-AS1在病人组织中的表达，探讨HIF1a-AS1对心血管疾病的影响；3) 利用分子生物学技术确定HIF1a-AS1的启动子，调控原件及其作用机制, 以期能确定一个新的心血管疾病相关lncRNA,为临床检验及治疗提供新靶点。